Respiratory Co-infection Research Articles

A Case of Triple Respiratory Coinfection: COVID-19, Enterovirus, and Parainfluenza

A Case of Triple Respiratory Coinfection: COVID-19, Enterovirus, and Parainfluenza

Paediatric iGAS Morbidity and Mortality in Ireland 2022-2023 episodic upsurge

Abstract There was an unseasonal upsurge in invasive Group A Streptococcal (iGAS) activity in Ireland during the 2022/2023 winter period. In particular, there was an increase in the proportion of paediatric infections and a rise in the age specific death rate for those under the age of 18, from 0.10 to 1.43 per 100,000. This review aimed to describe the demographic and clinical factors associated with paediatric iGAS infection during this upsurge. All iGAS cases under the age of 16 years, notified to Public Health between 1st October and 30th June 2023, were included. A review of hospital records for each case was conducted using a standardised electronic data collection proforma. Descriptive, univariate and multivariate analysis was conducted using SPSS statistical package. There was a total of 183 cases of iGAS notified during this upsurge in Ireland. A hospital chart review was conducted for 169 of these cases, giving a response rate of 92.3%. The median age was 4 years (range 0-15,) with 44.4% (75) having a previous healthcare attendance during their illness. Varicella coinfection occurred in 27.8% (47) of cases. There was respiratory viral coinfection in 40.8% (69) of cases, and this was significantly associated with an increased risk of death RR 6.49 (95% CI 4.45 - 29.08) p < 0.05. A respiratory site of infection was also significantly associated with an increased risk of death RR 10.13 (95% CI 2.23 - 45.95) p < 0.001. However, both factors did not remain significant once adjusted for age, sex, ethnicity and deprivation index. This national review demonstrated the significant burden of paediatric iGAS morbidity and mortality during this upsurge. A significant proportion of cases, 37.9% (64) were associated with vaccine preventable illness, with respiratory viral infections and a respiratory site of infection both being significantly associated with an increased risk of death. Key messages • A significant proportion of iGAS cases were associated with a vaccine preventable illness. • A respiratory site of iGAS infection was significantly associated with an increased risk of death in paediatric cases.

42 Clinical features and severity of COVID-19 with respiratory virus coinfections versus SARS-CoV-2 monoinfection in hospitalized children: A Canadian national surveillance study

Abstract Background The co-circulation of SARS-CoV-2 alongside other respiratory viruses has led to the risk of coinfections, potentially intensifying the severity of cases, especially in children. Objectives This study examined the epidemiology, clinical characteristics, and outcomes of SARS-CoV-2 respiratory virus coinfections in comparison to SARS-CoV-2 monoinfections in hospitalized children. Design/Methods A nationwide surveillance study was conducted to assess paediatric COVID-19-related hospitalizations across Canada from April 2020 to May 2022. Data were captured through two datasets covering ~90% of all Canadian tertiary-care paediatric beds: The Canadian Paediatric Surveillance Program and the Canadian Immunization Monitoring Program, ACTive. Coinfections were defined as the simultaneous detection of SARS-CoV-2 and ≥1 other respiratory virus. Severe infection was defined as intensive care, ventilatory, or hemodynamic support needs, organ systems complications, or death. Variables and outcomes were summarized and compared, and risk ratios were computed using Poisson regression, adjusting for age, gender, comorbid conditions, SARS-CoV-2 lineage, and vaccination status. Results Out of 1501 COVID-19-related hospitalizations, 163 (10.9%) had documented coinfections with 44/163 [27%] involving SARS-COV-2 plus ≥2 other respiratory viruses. The majority of SARS-CoV-2 monoinfections (1176/1501, 87.9%) and coinfections (139/163, 85.3%) belonged to the Omicron era (Figure A). RSV (66/163, 40.5%) and Enterovirus/rhinovirus (61/163, 37.4%) coinfections were the most common. Coinfection cases were significantly younger than monoinfection cases (median age 1.2 [IQR:0.3-3.3] vs 1.6 [IQR:0.3-7.0] years, p=0.04). Overall, severe disease was more common among cases with any coinfection (38.0%) than SARS-CoV-2 monoinfection (25.7%; adjusted risk ratio 1.45, 95% confidence interval 1.17-1.80) (Figure B). In particular, we observed that severe outcomes were significantly higher in SARS-CoV-2 coinfections compared to monoinfections during the Omicron era (Figure C-D). Overall, 26/61 (42.6%) Enterovirus/Rhinovirus and 20/66 (30.3%) RSV coinfections were associated with severe outcomes. Conclusion Children with documented coinfections had more severe respiratory disease compared to SARS-COV-2 monoinfections. However, children with severe COVID-19 may have been more likely tested for multiple viruses, leading to a risk of underestimation of coinfections among children with milder disease. Further work is needed to assess how different virus coinfections may affect children and which, if any, may be a predominant driver of disease severity. 1Severe disease was defined as intensive care, ventilatory, or hemodynamic support requirements, organ system complications, or death. 2Lineage was first assigned based on available genetic sequencing data. If missing, lineage was imputed based on the dominant circulating lineage at the provincial level according to the GISAID database.

A Machine Learning Approach to Determine Risk Factors for Respiratory Bacterial/Fungal Coinfection in Critically Ill Patients with Influenza and SARS-CoV-2 Infection: A Spanish Perspective.

Background: Bacterial/fungal coinfections (COIs) are associated with antibiotic overuse, poor outcomes such as prolonged ICU stay, and increased mortality. Our aim was to develop machine learning-based predictive models to identify respiratory bacterial or fungal coinfections upon ICU admission. Methods: We conducted a secondary analysis of two prospective multicenter cohort studies with confirmed influenza A (H1N1)pdm09 and COVID-19. Multiple logistic regression (MLR) and random forest (RF) were used to identify factors associated with BFC in the overall population and in each subgroup (influenza and COVID-19). The performance of these models was assessed by the area under the ROC curve (AUC) and out-of-bag (OOB) methods for MLR and RF, respectively. Results: Of the 8902 patients, 41.6% had influenza and 58.4% had SARS-CoV-2 infection. The median age was 60 years, 66% were male, and the crude ICU mortality was 25%. BFC was observed in 14.2% of patients. Overall, the predictive models showed modest performances, with an AUC of 0.68 (MLR) and OOB 36.9% (RF). Specific models did not show improved performance. However, age, procalcitonin, CRP, APACHE II, SOFA, and shock were factors associated with BFC in most models. Conclusions: Machine learning models do not adequately predict the presence of co-infection in critically ill patients with pandemic virus infection. However, the presence of factors such as advanced age, elevated procalcitonin or CPR, and high severity of illness should alert clinicians to the need to rule out this complication on admission to the ICU.

Changes in the Antimicrobial Resistance and Bacterial Epidemiology of Moraxella catarrhalis from Pediatric Community-Acquired Pneumonia Patients During the COVID-19 Pandemic: A 5-Year Study at a Tertiary Hospital of Southwest China.

This study aimed to assess the impact of the COVID-19 pandemic on Moraxella catarrhalis infections in pediatric patients hospitalized with community-acquired pneumonia (CAP). The epidemiological features and antimicrobial resistance (AMR) patterns of M. catarrhalis were compared between the pre-pandemic period (2018-2019) and during the pandemic (2020-2022). The results revealed a marked increase in the positivity rate of M. catarrhalis in 2020 and 2021 compared with the pre-pandemic years. The median age of the patients increased significantly in 2021 and 2022, while the proportion of male patients decreased substantially from 2019 to 2021. In addition, there were notable changes in the co-infections of Haemophilus influenzae, parainfluenza virus, and respiratory syncytial virus during the COVID-19 pandemic. The AMR profile of M. catarrhalis also changed significantly, showing increased resistance to ampicillin, but decreased resistance to trimethoprim-sulfamethoxazole and ofloxacin, and a lower proportion of multidrug-resistant isolates. Notably, ampicillin resistance increased among β-lactamase-producing isolates. Before the pandemic, the number and detection rate of isolates, along with resistance to ampicillin and trimethoprim-sulfamethoxazole, were seasonally distributed, peaking in autumn and winter. However, coinciding with local COVID-19 outbreaks, these indices sharply fell in February 2020, and the number of isolates did not recover during the autumn and winter of 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection landscape of M. catarrhalis in pediatric CAP patients, as evidenced by shifts in the detection rate, demographic characteristics, respiratory co-infections, AMR profiles, and seasonal patterns.

Exploring viral respiratory coinfections: Shedding light on pathogen interactions.

Exploring viral respiratory coinfections: Shedding light on pathogen interactions.

Clinical characteristics, treatment, and outcomes for elderly patients in a dedicated Covid-19 ward at a primary health care facility in western Norway: a retrospective observational study

BackgroundThe coronavirus pandemic has hit the oldest and frailest individuals hard, particularly patients and residents in nursing homes. In March 2020, we established a Covid-19 ward at a nursing home in Bergen, western Norway for elderly patients with Sars-CoV-2 infection and in the need of treatment and care in a primary health care facility. The aims of this study were to describe the organization of the ward, the clinical outcomes of infection, treatment, mortality rates in the population, the level of advanced care planning, and end-of-life care for those who died.MethodsWe present patient characteristics, outcomes, vaccination status, treatment, decisions regarding treatment intensity upon clinical deterioration, and mortality for the patients in the ward. Clinical factors possibly related to a fatal outcome were analysed with chi square test (categorical variables) or t-test (continuous variables).Results257 patients were included from March 2020 to April 2022. Fifty-nine patients (23.0%) developed respiratory failure. Ten patients (3.9%) were admitted to hospital. Advance care planning was undertaken for 245 (95.3%) of the patients. 30-day mortality rate decreased from 42 to 4% during the study period. Of the 29 (11.3%) patients who died, all were well alleviated in the terminal phase, and 26 (89.7%) of them had a Clinical Frailty Scale (CFS) value ≥ 7. A high score for CFS, respiratory failure and respiratory co-infection were significantly associated with Covid-19 related death within 30 days.ConclusionsCovid-19-related mortality markedly decreased during the study period, and a high score for CFS was related to a fatal outcome. Thorough planning of treatment intensity upon deterioration, low hospitalization rates, and good relief for those who died suggest that dedicated Covid-19 wards in nursing homes can provide good treatment for the patients and relieve other nursing homes and specialist health care services.

Patients with influenza admitted to a tertiary-care hospital in Riyadh between 2018 and 2022: characteristics, outcomes and factors associated with ICU admission and mortality

BackgroundInfluenza is a common cause of hospital admissions globally with regional variations in epidemiology and clinical profile. We evaluated the characteristics and outcomes of patients with influenza admitted to a tertiary-care center in Riyadh, Saudi Arabia.MethodsThis was a retrospective cohort of adult patients admitted with polymerase chain reaction-confirmed influenza to King Abdulaziz Medical City-Riyadh between January 1, 2018, and May 31, 2022. We compared patients who required intensive care unit (ICU) admission to those who did not and performed multivariable logistic regression to assess the predictors of ICU admission and hospital mortality.ResultsDuring the study period, 675 adult patients were hospitalized with influenza (median age 68.0 years, females 53.8%, hypertension 59.9%, diabetes 55.1%, and chronic respiratory disease 31.1%). Most admissions (83.0%) were in the colder months (October to March) in Riyadh with inter-seasonal cases even in the summertime (June to August). Influenza A was responsible for 79.0% of cases, with H3N2 and H1N1 subtypes commonly circulating in the study period. Respiratory viral coinfection occurred in 12 patients (1.8%) and bacterial coinfection in 42 patients (17.4%). 151 patients (22.4%) required ICU admission, of which 62.3% received vasopressors and 48.0% mechanical ventilation. Risk factors for ICU admission were younger age, hypertension, bilateral lung infiltrates on chest X-ray, and Pneumonia Severity Index. The overall hospital mortality was 7.4% (22.5% for ICU patients, p < 0.0001). Mortality was 45.0% in patients with bacterial coinfection, 30.9% in those requiring vasopressors, and 29.2% in those who received mechanical ventilation. Female sex (odds ratio [OR], 2.096; 95% confidence interval [CI] 1.070, 4.104), ischemic heart disease (OR, 3.053; 95% CI 1.457, 6.394), immunosuppressed state (OR, 7.102; 95% CI 1.803, 27.975), Pneumonia Severity Index (OR, 1.029; 95% CI, 1.017, 1.041), leukocyte count and serum lactate level (OR, 1.394; 95% CI, 1.163, 1.671) were independently associated with hospital mortality.ConclusionsInfluenza followed a seasonal pattern in Saudi Arabia, with H3N2 and H1N1 being the predominant circulating strains during the study period. ICU admission was required for > 20%. Female sex, high Pneumonia Severity Index, ischemic heart disease, and immunosuppressed state were associated with increased mortality.

277 Estimating the potential effect of Mycoplasma hyopneumoniae infection on swine sustainability

Abstract Mycoplasma hyopneumoniae is the primary causative agent of enzootic pneumonia, one of the most common bacterial pathogens affecting pigs and the main contributor to respiratory comorbidities. Infection with M. hyopneumoniae, commonly observed in growing pigs, results in decreased feed intake and an increase in the number of days to reach market weight. Based on extended days to market, pigs infected with M. hyopneumoniae will have a greater life cycle carbon emissions and water usage than that of non-infected pigs. However, the magnitude of additional carbon footprint and water use in pigs infected with M. hyopneumoniae has never been calculated. Therefore, the objective of this study was to estimate the potential variation in carbon emissions and water footprint generated by M. hyopneumoniae infected pigs. This study was conducted using data from previous publications on M. hyopneumoniae infected pigs in experimental and commercial conditions. The carbon footprint and water usage of pork production was obtained from the literature and was used as a baseline (3,470 kg of CO2 eq and 1,678 m3 water eq; both per 1,000 kg of pork carcass weight). The change in average daily gain was estimated and additional days on feed to reach market weight were used to calculate potential carbon and water impact for pigs infected with M. hyopneumoniae. The estimated carbon emissions and water usage of M. hyopneumoniae infected pigs increased in a range of 84.69 to 142.93 kg of CO2 eq/1,000 kg of pork carcass weight and 40.95 to 69.12 m3 eq/1,000 kg of pork carcass weight respectively, compared with the carbon emissions of non-infected pigs (Table 1). Results of this study showed an increased carbon footprint for M. hyopneumoniae infected pigs by 2 to 4% and water usage increased by 2.5 to 4.1% suggesting that the sustainability of pork production was negatively affected by this bacterial infection. Previous literature on the impact of controlling vaccine-preventable diseases has shown similar results for other swine respiratory pathogens. In addition, these data only included M. hyopneumoniae infected pigs, thus the effect of respiratory co-infections was not estimated and the impact on sustainability metrics may be greater than currently calculated. The application of sustainable practices in animal production, including disease prevention, is key to ensuring a secure food supply for future generations. The carbon and water footprints of swine production are measurements of sustainability, with average daily gain being an important factor.

Modeling the co-circulation of influenza and COVID-19 in Hong Kong, China

BackgroundAfter abandoning the zero-case strategy for COVID-19 in December 2022 in mainland China, the Hong Kong Special Administrative Region of China (HKSAR) has undergone an anticipated surge of the prevalence of COVID-19, as well as other influenzas, such as influenza A/H1N1, influenza A/H3N2, and influenza B as well. Noteworthy, people are usually concerned about the mutual influences between two families of respiratory viruses, like co-circulation or co-infection.MethodsWe fitted a unified model to weekly reported severe COVID-19 cases and the confirmed influenza A laboratory cases in HKSAR, respectively, using the R package POMP to obtain the best fitting and parameter estimates. The reconstructed transmission rates of the COVID-19 (/influenza A) versus the weekly reported influenza A (/COVID-19) confirmations between April 2022 and April 2024 were also compared.ResultsOur numerical results suggest that influenza confirmations remained either at a very low level or were absent before 2023, while starting from 2023, the influenza epidemic re-emerged as expected because of the resumption of international travels and other social communications. Besides, the peak of influenza cases in April 2023 favored the form of the peak of COVID-19 between May–June, 2023.Additionally, during the sudden abolishment of the zero-case policy in mainland China (December 2022 to January 2023), we estimated that there were approximately 381 cases imported from mainland China into HKSAR.ConclusionsWe estimated the potential number of imported COVID-19 severe cases from mainland China to Hong Kong and revealed some potential population-level interference between the two families of respiratory viruses.

Surge in Mycoplasma Pneumoniae infection and Respiratory Viruses Co-infection in Children With Community-Acquired Pneumonia in the Post-Pandemic.

During the COVID-19 pandemic, multifaceted non-pharmaceutical interventions have not only reduced the transmission of SARS-CoV2 but also affected the prevalence of other respiratory pathogens. With the lifting of many restrictions, a surge in cases of pneumonia in children has been reported in many hospitals in China. The study assessed the changes in pathogen and symptoms of children with community-acquired pneumonia (CAP) before and after the adjustments of prevention and control measures of epidemic and provided recommendations for CAP in children. Children diagnosed with CAP were enrolled in the study from 2022 to 2023. A cross-sectional retrospective study was conducted in a general hospital. We analyzed the data about demographic data, clinical symptoms, pathogens, and medical treatments. The Chi-square and Mann-Whitney U-test were used to assess the statistical significance of groups. We studied 1103 children, 339 in 2022 and 764 in 2023. Compared with children in 2022, more children were diagnosed with CAP in 2023 and these children had a higher body temperature and levels of CRP and PCT, which indicated these children got severe inflammation. The positive rate of the pathogen was also higher in 2023, especially the detective rate of Mycoplasma pneumoniae. The number of children infected with more than two pathogens was higher in 2023, especially those co-infected with the virus and M. Pneumoniae. Concerning the medicine therapy, the usage of β-lactam antibiotics, Macrolide antibiotics, and antiviral drugs kept rapid growth. After the adjustment of epidemic prevention and control policies in 2023, more children got CAP with severe clinical symptoms, and more antibiotics and antiviral drugs were used. Further study is needed to explore the reasons for the increase in children with CAP and to explore the rationality of treatment.

Inflammatory markers and lymphocyte subsets in COVID-19 patients with respiratory bacterial Co-infection: Clinical implications

Respiratory bacterial co-infections are frequently observed in COVID-19 patients. This retrospective study analysed clinical data from patients with COVID-19 and respiratory bacterial co-infections compared to those with COVID-19 alone. The findings suggest that inflammatory markers and lymphocyte subsets may be valuable for the early identification of co-infections in COVID-19 patients.

Associated factors of respiratory co-infection of COVID-19 and the impact of co-infection on SARS-CoV-2 viral load.

Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals are at an increased risk for co-infections. This retrospective study aims to expand the knowledge of associated factors of respiratory co-infection in SARS-CoV-2 positivity. A retrospective study was conducted to recruit fifty-five patients with laboratory-confirmed SARS-CoV-2 positivity. We additionally tested 29 other respiratory pathogens using RT-PCR assay for the same specimens tested for laboratory-confirmed SARS-CoV-2. Both univariate and multivariate analysis were performed to identify independent factors for co-infection. Cox regression was conducted to detect the association between co-infection and viral load after controlling other related factors. Among all the fifty-five COVID-19 patients, the rate of co-infection with at least one other respiratory pathogen was 76.4% (42/55). The rate of bacterial co-infections was 83.3% (35/42), among which Streptococcus pneumonia was the most common co-infection. Over 70% of neutrophils proportion (OR: 4.563; 95% CI: 1.116-18.648) was an independently associated factor for bacterial co-infection, whereas fever (OR: 4.506; 95% CI: 1.044-19.441) and chest tightness (OR: 0.106; 95% CI: 0.015-0.743) for viral co-infection. The strongest promotion of SARS-CoV-2 viral decreasing load was detected from co-infection of only viruses (HR: 4.039; 95% CI: 1.238-13.177), and the weakest was found from co-infection of only bacteria (HR: 2.909; 95% CI: 1.308-6.472). Various co-infections variously promote SARS-CoV-2 viral decreasing load. Timely identification of co-infections aggressively contributes to COVID-19 patient management.

Prevalence of Co-Infections in Primary Care Patients with Medically Attended Acute Respiratory Infection in the 2022/2023 Season.

In the post-pandemic period, an endemic circulation of respiratory viruses has been re-established. Respiratory viruses are co-circulating with SARS-CoV-2. We performed a retrospective analysis of co-infections in primary care patients with medically attended acute respiratory infections (MAARI) who consulted from week 40/2022 to week 39/2023 and were tested for a panel of respiratory viruses. Out of 2099 samples tested, 1260 (60.0%) were positive for one virus. In 340 samples, co-infection was detected: two viruses in 281 (13.4%), three viruses in 51 (2.4%), and four viruses in eight (0.4%) samples. Respiratory viruses co-infected the patients with MAARI at very different rates. The lowest rates of co-infections were confirmed for influenza B (13.8%) and influenza A (22.9%) and the highest for human bocaviruses (84.0%) and human parechoviruses (82.1%). Co-infections were detected in 28.2% of SARS-CoV-2 positive samples. SARS-CoV-2 has never been co-infected with influenza B virus, enterovirus or adenovirus, although the latter was found as a co-infecting virus with all other respiratory viruses tested. The rate of co-infections decreased significantly with increasing age (p-value 0.000), and no difference was found regarding gender (p-value 0.672). It is important to understand the epidemiology of respiratory co-infections for prevention and management decisions in patients with MAARI.

Epidemiology and Management of Pediatric Group A Streptococcal Pneumonia With Parapneumonic Effusion: An Observational Study.

During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.

Potential role of alveolar macrophages in HIV persistence and lung disease

While antiretroviral therapy (ART) has revolutionized the management of human immunodeficiency virus (HIV) and has enabled people living with HIV (PLWH) to achieve near-normal life expectancies, an HIV cure remains elusive due to the presence of HIV reservoirs. Furthermore, compared with individuals in the general population, PLWH support a higher burden of multimorbidity, including pulmonary diseases of both an infectious and non-infection nature, which may be a consequence of the formation of HIV reservoirs. Their gut, lymph nodes, brain, testes and lungs constitute important anatomic sites for the reservoirs. While CD4+ T-cells, and particularly memory CD4+ T-cells, are the best characterized cellular HIV reservoirs, tissue resident macrophages (TRM) and alveolar macrophages (AM) also harbor HIV infection. AM are the most abundant cells in bronchoalveolar (BAL) fluid in healthy conditions, and act as sentinels in the alveolar space by patrolling and clearing debris, microbes and surfactant recycling. Long-lived tissue-resident AM of embryonic origin have the capacity of self-renewal without replenishment from peripheral monocytes. As in other tissues, close cell-cell contacts in lungs also provide a milieu conducive for cell-to-cell spread of HIV infection and establishment of reservoirs. As lungs are in constant exposure to antigens from the external environment, this situation contributes to pro-inflammatory phenotype rendering pulmonary immune cells exhausted and senescent-an environment facilitating HIV persistence. Factors such as tobacco and e-cigarette smoking, lung microbiome dysbiosis and respiratory co-infections further drive antigenic stimulation and HIV replication. HIV replication, in turn, contributes to ongoing inflammation and clonal expansion. Herein, the potential role of AM in HIV persistence is discussed. Furthermore, their contribution towards pulmonary inflammation and immune dysregulation, which may in turn render PLWH susceptible to chronic lung disease, despite ART, is explored. Finally, strategies to eliminate HIV-infected AM are discussed.

Potential role of alveolar macrophages in HIV persistence and lung disease.

While antiretroviral therapy (ART) has revolutionized the management of human immunodeficiency virus (HIV) and has enabled people living with HIV (PLWH) to achieve near-normal life expectancies, an HIV cure remains elusive due to the presence of HIV reservoirs. Furthermore, compared with individuals in the general population, PLWH support a higher burden of multimorbidity, including pulmonary diseases of both an infectious and non-infection nature, which may be a consequence of the formation of HIV reservoirs. Their gut, lymph nodes, brain, testes and lungs constitute important anatomic sites for the reservoirs. While CD4+ T cells, and particularly memory CD4+ T cells, are the best characterized cellular HIV reservoirs, tissue resident macrophages (TRM) and alveolar macrophages (AM) also harbor HIV infection. AM are the most abundant cells in bronchoalveolar (BAL) fluid in healthy conditions, and act as sentinels in the alveolar space by patrolling and clearing debris, microbes and surfactant recycling. Long-lived tissue-resident AM of embryonic origin have the capacity of self-renewal without replenishment from peripheral monocytes. As in other tissues, close cell-cell contacts in lungs also provide a milieu conducive for cell-to-cell spread of HIV infection and establishment of reservoirs. As lungs are in constant exposure to antigens from the external environment, this situation contributes to pro-inflammatory phenotype rendering pulmonary immune cells exhausted and senescent-an environment facilitating HIV persistence. Factors such as tobacco and e-cigarette smoking, lung microbiome dysbiosis and respiratory coinfections further drive antigenic stimulation and HIV replication. HIV replication, in turn, contributes to ongoing inflammation and clonal expansion. Herein, the potential role of AM in HIV persistence is discussed. Furthermore, their contribution towards pulmonary inflammation and immune dysregulation, which may in turn render PLWH susceptible to chronic lung disease, despite ART, is explored. Finally, strategies to eliminate HIV-infected AM are discussed.

Acute Respiratory Tract Infections in Pediatric Populations of Slum Areas: Navigating Challenges and Dynamics of Immune Responses.

The study presents a thorough examination of immune responses in pediatric populations within slum areas, specifically addressing respiratory infections. It explores the impact of slum conditions on respiratory health, detailing the epidemiology of infections, including common pathogens and environmental factors. The review delves into the etiology, clinical manifestations, and challenges associated with viral respiratory infections, co-infections, and complications in slum environments. The discussion extends to immune responses in pediatric respiratory infections, emphasizing unique challenges in diagnosis and treatment within slum areas. Prevention and intervention strategies are highlighted, encompassing vaccination programs, health education, and improving living conditions. It underscores the importance of targeted interventions, accounting for socio-economic factors, community-based strategies, and culturally sensitive approaches. It proposes the exploration of novel approaches and the development of vaccines tailored to prevalent respiratory pathogens in slum settings. Furthermore, the feasibility and impact of routine immunization programs, emphasizing accessibility, acceptance, and long-term sustainability are explored. It advocates strengthening primary healthcare systems, investing in healthcare workforce training, and improving diagnostic facilities. The potential of digital health technologies in enhancing surveillance, early detection, and the development of mobile applications or telemedicine platforms is discussed. In conclusion, the study emphasizes the multifaceted challenges faced by children in slum areas regarding respiratory infections, necessitating informed, interdisciplinary interventions. Addressing healthcare disparities, improving living conditions, and enhancing vaccination coverage are deemed crucial for mitigating the burden of respiratory infections. This review calls for collaborative efforts among researchers, healthcare professionals, policymakers, and community stakeholders to develop sustainable solutions for enhanced respiratory health in slum-dwelling pediatric populations.

Impact of antibiotic therapy in patients with respiratory viral infections: a retrospective cohort study

Objectives The impact of antibiotics in patients with positive polymerase chain reaction (PCR) for respiratory viruses without evidence of a respiratory bacterial co-infection is largely unknown. The aim of this study was to assess the association of antibiotics on 30-day mortality and length of hospital stay in patients with an acute respiratory infection and PCR documented presence of respiratory viruses. Methods We conducted a retrospective cohort study of adult patients admitted to hospital between 2012 and 2021 with positive PCR for influenza virus (H3N2, H1N1, influenza B), respiratory syncytial virus, human metapneumovirus or severe acute respiratory syndrome coronavirus 2. We used logistic regression, the Kaplan–Meier estimator and Poisson’s regression to assess the impact of antibiotic therapy on outcomes. Results Among 3979 patients, 67.7% received antibiotics. In adjusted analyses, antibiotics initiated in the emergency department (adjusted OR 1.23, 95% CI 0.77–1.96) and days of antibiotic therapy (adjusted OR per day of therapy 0.98, 95% CI 0.95–1.00) had no significant impact on mortality, whereas antibiotics initiated later during admission (adjusted OR 2.25, 95% CI 1.26–4.02) was associated with increased mortality. Patients prescribed antibiotics had longer duration of hospital admission. Conclusions We observed no protective association between in-hospital antibiotic therapy and outcomes, suggesting overuse of antibiotics in respiratory infections with proven respiratory viruses. A restrictive antibiotic strategy may be warranted.

Evaluation of the Characteristics of Respiratory Viruses and Coinfections in Hospitalized Children during the COVID-19 Pandemic

Abstract Objective Studies have shown that more than one viral agent is not uncommonly detected simultaneously in respiratory tract infections of children. The aim of this study was to analyze our single-center experience with the seasonal distribution, clinical and laboratory outcomes of respiratory viruses, and coinfections in hospitalized children during the coronavirus disease 2019 (COVID-19) pandemic. Methods During the pandemic period of June 1, 2021 to February 1, 2022, 156 pediatric patients hospitalized with non-COVID-19 respiratory tract infections were retrospectively analyzed. Among these children, 92 were found to be positive for respiratory pathogens. These children's ages, genders, polymerase chain reaction results, and blood parameters were analyzed. Results The median age of the patients was 8 months (10 days–17.1 years) and 63% were male. A total of 16.3% of the patients were neonates (0–28 days), 55.4% were infants (1–24 months), 16.3% were preschool (2–5 years), and 12% were school-aged (5–18 years); 73.9% of the patients were hospitalized in the pediatric ward, 16.3% in the neonatal intensive care unit, and 9.8% in the pediatric intensive care unit. In 76.5% of hospitalized patients, only one pathogen was identified. Respiratory syncytial virus was detected as a causative agent of either mono- or coinfections in 78.4% of all patients. There was no statistical difference between inflammatory parameters in the patients infected with single or multiple viral agents. Conclusion As a result of the precautions taken during the pandemic, we found that the viral distribution of respiratory tract infections changed. In addition, we believe that hematological parameters are not useful for distinguishing between mono- and coinfections.